The promise of proteomics—measuring protein levels—as a tool for assessing risk of heart attacks and strokes was highlighted in a new study in the Journal of the American Medical Association.
In this study, published this week, researchers used an innovative protein measurement assay developed by healthcare technology company SomaLogic to detect 1,130 different proteins in the plasma of nearly 2,000 individuals already diagnosed with coronary heart disease. They discovered that high levels of nine proteins in the plasma of a person with stable coronary heart disease more accurately predicted the risk of that person within four years having a heart attack or stroke, developing heart failure or dying than measuring traditional risk factors such as high blood pressure, high cholesterol and smoking status.
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Proteomics may be more accurate than assessing those traditional risk factors because “proteins are one step closer to the disease itself,” explained Dr. Peter Ganz, the study’s principal investigator and a professor of medicine at the University of California, San Francisco, School of Medicine.
“You need something beyond risk factors to see if these risk factors are inflicting any damage. Proteins are one step closer to the actual event,” said Ganz. He explained that blood pressure or cholesterol readings may not always be accurate benchmarks of cardiac risk because the sickest patients are often treated the most aggressively for those conditions, which may result in those patients having lower blood pressure or cholesterol numbers than those individuals who are not as ill.
Instead of measuring protein levels directly, SomaLogic’s assay takes a different approach by using aptamers, which are single-strand DNA molecules that bind to proteins. The assay uses more than 1,000 different DNA molecules, and each one binds to a different protein, explained Dr. Stephen A. Williams, SomaLogic’s chief medical officer.
“The beauty of this approach is that once the aptamer binds to the protein, you can quantify the amount of protein indirectly,” Ganz said. “It converts protein measurement to a DNA measurement, and measuring DNA is easy—all you need is a chip. … It’s a very clever technology.”
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Unlike other methods for measuring protein levels, such as mass spectrometry or antibody arrays, the SomaLogic assay can quickly measure a large amount of samples and detect low levels of proteins, noted Ganz.
Because most of the individuals in the study were older men, the next step is for researchers to evaluate the usefulness of the protein assay for predicting the risk of heart attacks and strokes in a more demographically diverse population, Ganz said. Investigators also need to research the predictive ability of the protein assay for people who do not already have cardiovascular disease, as well as for individuals who have chronic conditions such as kidney disease, Ganz noted.
“We are also looking at proteins that are predictive of successful response to treatment,” Ganz added.
Williams sees proteomics as a powerful new tool that will take its place alongside gene sequencing for assessing a person’s risk for specific diseases, as well as the likelihood of a patient responding to a specific therapy.
“We think it is the perfect complement to genomics,” Williams said. “The gene is like a house blueprint, but if you want to know if the house is on fire, a blueprint is not much help. You really need a smoke detector.”
Based on the study results, SomaLogic is developing a diagnostic test for cardiovascular diagnostic test that will be available later this year in SomaLogic’s laboratory in Boulder, Colorado. The company also is studying the usefulness of proteomics for assessing disease risk in people with liver fibrosis and lung cancer.
“In the end, we want to have a metabolic health dashboard for clinicians who have to manage patients with multiple risk factors,” Williams said.
Photo: Flickr user Ged Carroll
